Fibrous, Fibrohistiocytic, and Giant Cell Tumor Malignancies

By admin On Apr 13, 2023

Ovid: Oncology and Basic Science

Editors: Tornetta, Paul; Einhorn, Thomas A.; Damron, Timothy A.

Title: Oncology and Basic Science, 7th Edition

> Table of Contents > Section
II – Specific Bone Neoplasms and Simulators > 6 – Bone Sarcomas >
6.4 – Fibrous, Fibrohistiocytic, and Giant Cell Tumor Malignancies

6.4

Fibrous, Fibrohistiocytic, and Giant Cell Tumor Malignancies

Hannah D. Morgan

Fibrosarcoma, malignant fibrous histiocytoma (MFH) of
bone, and malignancy in giant cell tumor (GCT) are three relatively
rare bone sarcomas that tend to be of high grade. All are found
primarily around the knee. MFH and malignancy in GCT of bone may be
primary or secondary malignancies. Malignancy in GCT is the current
World Health Organization (WHO) terminology for what has also been
referred to as malignant giant cell tumor or dedifferentiated giant
cell tumor. MFH is now referred to as pleomorphic sarcoma not otherwise
specified (NOS) as it is thought to

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represent a final common pathway toward dedifferentiation for many sarcomas.

Pathogenesis

Etiology

Fibrosarcoma
- Malignant spindle cell tumor with fibroblastic differentiation and a collagenous intercellular background
MFH
- Malignant mesenchymal neoplasm of histiocytic origin
- 72% primary; 28% secondary
- Conditions associated with secondary
  form: bone infarction, fibrous dysplasia, intraosseous lipoma, Paget’s
  disease, prolonged steroid use, hematopoietic malignancy, history of
  radiation therapy, and possibly presence of metallic orthopaedic
  implant (controversial)
Malignancy in GCT
- Primary malignancy in GCT: high-grade sarcoma arising beside or within a conventional GCT of bone
- Secondary malignancy in GCT: high-grade
  sarcoma arising at the site of a previously treated conventional GCT
  (either with surgery alone or with radiation therapy); tumors often
  multiply recurrent prior to diagnosis of malignancy

Epidemiology

Fibrosarcoma
- <5% of malignant bone tumors; may be lower as more cases are diagnosed as fibroblastic osteosarcoma or MFH
- Male:female 1:1
- Most patients second through seventh decade
- Arises in metaphysis, most commonly around the knee
MFH
- <2% of malignant bone tumors
- Male:female 3:2
- All ages affected, but majority >40 years old
- 75% affect ends of long tubular bones; 50% about the knee
Malignant GCT
- Very rare: 1% to 2% of all GCT of bone
- Primary malignant GCT: male > female
- Secondary malignant GCT: male:female 1:1
- Average age: 45 to 50 years
- Secondary malignant GCTs
  - Typically occur >3 years after treatment of original tumor
  - Average latent period: 9 years
- Majority of tumors occur about knee, as for benign GCT of bone.

Figure 6.4-1 Fibrosarcoma of bone.

Pathophysiology

Fibrosarcoma
- Uniform fibroblast-like spindle cells arranged in parallel bundles with intercellular collagen in herringbone pattern (Fig 6.4-1)
- One study found 22q aberration leading to increased platelet-derived growth factor beta (PDGF-β).
MFH
- Plump malignant spindle-shaped cells in
  sheets and storiform patterns with granular eosinophilic cytoplasm; may
  have cytoplasmic vacuoles; marked nuclear atypia and numerous atypical
  mitoses (Fig. 6.4-2)
Malignant GCT
- High-grade lesions that usually exhibit a
  continuum of microscopic change between areas of conventional benign
  GCT of bone (multinucleated giant cells with benign spindle cell
  stroma) and areas of high-grade sarcoma (usually pleomorphic sarcoma or
  osteosarcoma)
- May have p53 or H-ras molecular abnormality

Figure 6.4-2
Malignant fibrous histiocytoma. An anaplastic tumor exhibits spindle
cells, plump lipid-laden histiocytes, tumor giant cells, an abnormal
mitosis (center), and a mild chronic inflammatory infiltrate. (From
Rubin E, Farber JL. Pathology, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999.)

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Classification

Fibrosarcoma
- May be low- or high-grade malignancy
MFH
- Aggressive high-grade tumor
- Pleomorphic, histiocytic, giant cell, myxoid, and inflammatory variants described
Malignant GCT
- High-grade lesions
- Primary malignant GCT: occurs de novo
- Secondary malignant GCT: occurs following latent period after treatment of benign GCT of bone with surgery and/or radiation

Diagnosis

Physical Examination and History

Clinical Features

Pain and swelling are most common; all may present with pathologic fracture.

Fibrosarcoma
- Nothing unique
MFH
- Palpable tender mass
- Symptoms develop over months to years.
- Pathologic fracture in 30% to 50% of patients
Malignant GCT
- Primary malignant GCT: symptoms present for an average of 12 months
- Secondary malignant GCT: symptoms present for an average of 7 months

Radiologic Features

Radiographs
- Show destructive lytic lesion, often in
  metaphyseal area; may have diaphyseal or epiphyseal extension; with or
  without pathologic fracture
Computed tomography (CT) scan
- Bone involvement
  - Assess intraosseous and extraosseous extent of tumor
  - Best test for demonstrating cortical involvement
- Chest CT
  - Used to look for pulmonary metastases in high-grade lesions
Magnetic resonance imaging (MRI)
- Best test for evaluating marrow involvement and associated soft tissue mass, which is frequently present with all of these
- Can also demonstrate cortical involvement
- Evaluate relationship of tumor to adjacent neurovascular structures
Bone scan
- Look for osseous metastasis; determine extent of bony involvement of tumor
Positron emission tomography: investigational

Treatment

Surgical Indications and Contraindications

Surgical and Nonoperative Options

All high-grade fibrosarcomas, MFH, and malignant GCT of
bone should be treated surgically with the intent of achieving a wide
surgical resection, either by way of limb-sparing surgery or
amputation. Neoadjuvant and adjuvant chemotherapy (often doxorubicin
[Adriamycin]-based) and radiation therapy may enhance tumor control and
are supported by univariate analysis of retrospective
multi-institutional survey data.

Preoperative Planning (also see Chapter 4, Treatment Principles)

Appropriate imaging studies should be obtained to
determine the extent of resection that is necessary. Any allograft or
orthopaedic implants that will be used for reconstruction should be
ordered. The patient should have a preoperative medical work-up when
appropriate, and blood products should be ordered if significant
intraoperative blood loss is anticipated. Surgical goals and
approaches, techniques, and complications are covered in Chapter 4.

Results and Outcome (Prognosis)

Fibrosarcoma
- True prognosis difficult to determine, as many tumors once labeled fibrosarcoma are actually MFH of bone
- Low grade: 10-year survival estimated to be 80%; metastasis in 5% to 20% of patients
- High grade: 10-year survival 40% or less; metastasis in 55% to 65% of patients
MFH
- Estimated 50% to 60% 5-year survival
- Younger patients and those receiving chemotherapy have better prognosis.
Malignancy in GCT
- Approximately 50% 5-year survival
- Chemotherapy may offer increased survival in some patients, but no randomized prospective trials have been done.
- Postradiation secondary malignant GCT has worse prognosis.

Postoperative Management

Same as for all bone sarcomas (see Chapter 4).